Manifestations Of Disease Research Articles

Prevalence and Characterization of NOTCH2NLC GGC Repeat Expansions in Koreans: From a Hospital Cohort Analysis to a Population-Wide Study.

GGC repeat expansions in the NOTCH2NLC gene are associated with a broad spectrum of progressive neurologic disorders, notably, neuronal intranuclear inclusion disease (NIID). We aimed to investigate the population-wide prevalence and clinical manifestations of NOTCH2NLC-related disorders in Koreans. We conducted a study using 2 different cohorts from the Korean population. Patients with available brain MRI scans from Seoul National University Hospital (SNUH) were thoroughly reviewed, and NIID-suspected patients presenting the zigzag edging signs underwent genetic evaluation for NOTCH2NLC repeats by Cas9-mediated nanopore sequencing. In addition, we analyzed whole-genome sequencing data from 3,887 individuals in the Korea Biobank cohort to estimate the distribution of the repeat counts in Koreans and to identify putative patients with expanded alleles and neurologic phenotypes. In the SNUH cohort, among 90 adult-onset leukoencephalopathy patients with unknown etiologies, we found 20 patients with zigzag edging signs. Except for 2 diagnosed with fragile X-associated tremor/ataxia syndrome and 2 with unavailable samples, all 16 patients (17.8%) were diagnosed with NIID (repeat range: 87-217). By analyzing the Korea Biobank cohort, we estimated the distribution of repeat counts and threshold (>64) for Koreans, identifying 6 potential patients with NIID. Furthermore, long-read sequencing enabled the elucidation of transmission and epigenetic patterns of NOTCH2NLC repeats within a family affected by pediatric-onset NIID. This study presents the population-wide distribution of NOTCH2NLC repeats and the estimated prevalence of NIID in Koreans, providing valuable insights into the association between repeat counts and disease manifestations in diverse neurologic disorders.

Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection

Chagasic chronic cardiomyopathy (CCC) is the primary clinical manifestation of Chagas disease (CD), caused by Trypanosoma cruzi. Current therapeutic options for CD are limited to benznidazole (Bz) and nifurtimox. Amiodarone (AMD) has emerged as most effective drug for treating the arrhythmic form of CCC. To address the effects of Bz and AMD we used a preclinical model of CCC. Female C57BL/6 mice were infected with T. cruzi and subjected to oral treatment for 30 consecutive days, either as monotherapy or in combination. AMD in monotherapy decreased the prolonged QTc interval, the incidence of atrioventricular conduction disorders and cardiac hypertrophy. However, AMD monotherapy did not impact parasitemia, parasite load, TNF concentration and production of reactive oxygen species (ROS) in cardiac tissue. Alike Bz therapy, the combination of Bz and AMD (Bz/AMD), improved cardiac electric abnormalities detected T. cruzi-infected mice such as decrease in heart rates, enlargement of PR and QTc intervals and increased incidence of atrioventricular block and sinus arrhythmia. Further, Bz/AMD therapy ameliorated the ventricular function and reduced parasite burden in the cardiac tissue and parasitemia to a degree comparable to Bz monotherapy. Importantly, Bz/AMD treatment efficiently reduced TNF concentration in the cardiac tissue and plasma and had beneficial effects on immunological abnormalities. Moreover, in the cardiac tissue Bz/AMD therapy reduced fibronectin and collagen deposition, mitochondrial damage and production of ROS, and improved sarcomeric and gap junction integrity. Our study underlines the potential of the Bz/AMD therapy, as we have shown that combination increased efficacy in the treatment of CCC.

Caesalpinia sappan Reduce Fever with An Anti-inflammatory and Antioxidant Mechanism: A Review

<p><em><span lang="EN-US">Caesalpinia sappan L</span></em><span lang="EN-US"> (Sappan wood) is an herbal plant that has long been trusted by the public as an herbal medicine for tuberculosis, diarrhea, dysentery, skin infections, anemia, and other diseases by utilizing the decoction of <em>C.sappan</em>. Sappan wood is an herbal plant widely used as a raw material for traditional medicinal products. Sappan wood has been reported to have substantial pharmacological effects in analgesic, antioxidant, antibacterial, anti-inflammatory, and anti-viral. Fever is a clinical manifestation of certain conditions or diseases characterized by increased body temperature above the normal range (36.5–37.5 °C). Many studies declare that antioxidant and anti-inflammatory activity in <em>C.sappan</em> reduces oxidative stress and pro-inflammatory cytokines. This literature review shows that the antioxidant and anti-inflammatory properties of <em>C.sappan</em> are linked to fever as a sign of illness. Literature review using the last ten years' Scopus, ScienceDirect, and Pubmed databases. There are as many as 20 journals regarding sappan wood's antioxidant and anti-inflammatory effects. Sappan wood has been shown to have an antioxidant effect by lowering reactive oxygen species levels via SOD, GPx, or CAT markers. It inhibits inflammation cytokines such as IL-1, IL-6, TNF-</span><span lang="EN-US">𝝰</span><span lang="EN-US">, and INF produced during fever. Sappan wood also has an anti-inflammatory effect by inhibiting PGE2 production when someone has a fever. The findings of our review state that <em>C.sappan</em> can be used to treat fever for both of these reasons. The use of <em>C.sappan</em> as a component in producing traditional health beverages has potential.</span></p>

Gait Variability as a Potential Motor Marker of Cerebellar Disease—Relationship between Variability of Stride, Arm Swing and Trunk Movements, and Walking Speed

Excessive stride variability is a characteristic feature of cerebellar ataxias, even in pre-ataxic or prodromal disease stages. This study explores the relation of variability of arm swing and trunk deflection in relationship to stride length and gait speed in previously described cohorts of cerebellar disease and healthy elderly: we examined 10 patients with spinocerebellar ataxia type 14 (SCA), 12 patients with essential tremor (ET), and 67 healthy elderly (HE). Using inertial sensors, recordings of gait performance were conducted at different subjective walking speeds to delineate gait parameters and respective coefficients of variability (CoV). Comparisons across cohorts and walking speed categories revealed slower stride velocities in SCA and ET patients compared to HE, which was paralleled by reduced arm swing range of motion (RoM), peak velocity, and increased CoV of stride length, while no group differences were found for trunk deflections and their variability. Larger arm swing RoM, peak velocity, and stride length were predicted by higher gait velocity in all cohorts. Lower gait velocity predicted higher CoV values of trunk sagittal and horizontal deflections, as well as arm swing and stride length in ET and SCA patients, but not in HE. These findings highlight the role of arm movements in ataxic gait and the impact of gait velocity on variability, which are essential for defining disease manifestation and disease-related changes in longitudinal observations.

Primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is arare genetic disorder with avariable clinical phenotype that is accompanied by reduced motility of the cilia in the respiratory tract and numerous other organs. This leads to various characteristic symptoms and disease manifestations, primarily affecting the lungs (chronic persistent productive cough, bronchiectasis), the nose and paranasal sinuses (chronic persistent rhinitis or rhinosinusitis) as well as the middle ear (chronic otitis media, middle ear effusion). Moreover, PCD is associated with impaired fertility or lateralization defects (situs anomalies, congenital heart defects). The diagnostics of PCD are complex and require acombination of several sophisticated instrument-based diagnostic procedures. Through thorough history taking and evaluation, suspected cases can be comparatively well identified based on typical clinical features and referred to further diagnostics. In recent years, molecular genetic analysis through panel diagnostics or whole exome and whole genome sequencing, has gained in importance as this enables affected individuals to participate in disease-specific and genotype-specific clinical trials. Although the current treatment is purely symptomatic, the earliest possible diagnosis is crucial for connecting patients to specialized PCD centers, which can have asignificant impact on the clinical course of the affected individuals.

Dietary habits and compliance with dietary guidelines in patients with established cardiovascular disease.

Unhealthy dietary habits are an important risk factor for cardiovascular disease (CVD) and adopting a healthy diet is a central recommendation in CVD prevention. This study assessed the dietary habits of patients with established CVD, their compliance to dietary guidelines, and the relationship between guideline-compliance and recurrent cardiovascular event risk. 2656 patients with established CVD from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART) prospective cohort study, were included between 1996 and 2022. Data on dietary intake was retrospectively collected for all participants in December 2022 using a 160-item food frequency questionnaire. Compliance with dietary guidelines was quantified using an amended version of the Dutch Healthy Diet 2015 (DHD-15) index (range: 0-135). Cox proportional hazard models were used to quantify the relationship with cardiovascular events (stroke and myocardial infarction). Among 2656 CVD patients (77% male, mean age 59 ± 9 years), median energy intake was 1922 [IQR: 1536-2351] kcal/day. The median DHD-15 index was 81.7 [IQR 71.2-92.0], with high compliance scores for recommendations on legumes and fish, and low scores for recommendations on whole grains, red meat, processed meat, and dairy. A higher DHD-15 score was associated with lower stroke risk (HR 0.78, 95% CI 0.66-0.92 per 10-point increase) but not with myocardial infarction. Compliance with dietary guidelines was suboptimal in patients with established CVD. High compliance was associated with a clinically significant reduction in stroke risk in patients with established CVD, emphasizing the importance of dietary counseling.

Cardiac comorbidities in McArdle disease: case report and systematic review.

Myophosphorylase deficiency, also known as McArdle disease or Glycogen Storage Disease type V (GSD-V), is an autosomal recessive metabolic myopathy that results in impaired glycogen breakdown in skeletal muscle. Despite being labelled as a "pure myopathy," cardiac involvement has been reported in some cases, including various cardiac abnormalities such as electrocardiographic changes, coronary artery disease, and cardiomyopathy. Here, we present a unique case of a 72-year-old man with GSD-V and both mitral valvulopathy and coronary artery disease, prompting a systematic review to explore the existing literature on cardiac comorbidities in McArdle disease. Our systematic literature revision identified 7 case reports and 1 retrospective cohort study. The case reports described 7 GSD-V patients, averaging 54.3years in age, mostly male (85.7%). Coronary artery disease was noted in 57.1% of cases, hypertrophic cardiomyopathy in 28.5%, severe aortic stenosis in 14.3%, and genetic dilated cardiomyopathy in one. In the retrospective cohort study, five out of 14 subjects (36%) had coronary artery disease. Despite McArdle disease primarily affecting skeletal muscle, cardiac involvement has been observed, especially coronary artery disease, the frequency of which was moreover found to be higher in McArdle patients than in the background population in a previous study from a European registry. Exaggerated cardiovascular responses during exercise and impaired glycolytic metabolism have been speculated as potential contributors. A comprehensive cardiological screening might be recommended for McArdle disease patients to detect and manage cardiac comorbidities. A multidisciplinary approach is crucial to effectively manage both neurological and cardiac aspects of the disease and improve patient outcomes. Further research is required to establish clearer pathophysiological links between McArdle disease and cardiac manifestations in order to clarify the existing findings.

Cadmium Exposure: Mechanisms and Pathways of Toxicity and Implications for Human Health

Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca2+ signaling, interference with cellular signaling pathways, and epigenetic modifications. By detailing the absorption, distribution, metabolism, and excretion (ADME) of Cd, alongside its interactions with cellular components such as mitochondria and DNA, this paper highlights the extensive damage caused by Cd2+ at the cellular and tissue levels. The role of Cd in inducing oxidative stress—a pivotal mechanism behind its toxicity—is discussed with emphasis on how it disrupts the balance between oxidants and antioxidants, leading to cellular damage and apoptosis. Additionally, the review covers Cd’s impact on signaling pathways like Mitogen-Activated Protein Kinase (MAPK), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor Protein 53 (p53) pathways, illustrating how its interference with these pathways contributes to pathological conditions and carcinogenesis. The epigenetic effects of Cd, including DNA methylation and histone modifications, are also explored to explain its long-term impact on gene expression and disease manifestation. This comprehensive analysis not only elucidates the mechanisms of Cd toxicity but also underscores the critical need for enhanced strategies to mitigate its public health implications.

Systematic review and meta-analysis: proton pump inhibitors slightly decrease the severity of chronic cough

The Montreal consensus recognizes chronic cough as an extra-esophageal manifestation of gastroesophageal reflux disease. We performed a meta-analysis to assess the effects of acid-suppressive medications in adults with non-specific chronic cough. The protocol was registered on PROSPERO (CRD42022368769). Placebo-controlled randomized trials evaluating the impact of acid-suppressive medications on persistent cough were included. The systematic search was performed on the 1st of November 2022 in three databases. A random-effects model was used for the calculations. The effect size was the standardized mean difference (SMD) with 95% confidence interval (CI). A total number of 11 double-blinded placebo-controlled randomized trials were included in the meta-analysis. Data showed that compared to placebo, PPIs decreased the severity of cough (SMD 0.33; CI 0.05; 0.61). Therapeutic response was not different in patients with non-specific chronic cough only, compared to those with laryngopharyngeal reflux. Prolonged treatment durations did not result in greater symptomatic improvement, with SMD 0.33 (CI − 0.22; 0.88), 0.31 (CI − 1.74; 2.35), 0.32 (CI − 0.29; 0.93) and 0.34 (CI − 0.16; 0.85), following 4, 6, 8 and 12 weeks of treatment, respectively. The pooled analysis of the improvement in quality of life with PPIs found an SMD of 0.39 (CI − 0.51; 1.29). PPIs mildly decrease the severity of non-specific chronic cough, irrespective of treatment duration.

Poly (ADP-ribose) Polymerase-1 modulations in the genesis of thrombosis.

Thrombosis, a coagulation disorder, occurs due to altered levels of coagulation, fibrinolytic and immune factors, which are otherwise known to maintain hemostasis in normal physiological conditions. Here, we review the direct and indirect participation of a multifunctional nuclear enzyme poly (ADP-ribose) polymerase-1 (PARP1) in the expression of key genes and cellular processes involved in thrombotic pathogenesis. PARP1 biological activities range from maintenance of genomic integrity, chromatin remodeling, base excision DNA repair, stress responses to cell death, angiogenesis and cell cycle pathways. However, under homeostatic imbalances, PARP1 activities are linked with the pathogenesis of diseases, including cancer, aging, neurological disorders, and cardiovascular diseases. Disease-associated distressed cells employ a variety of PARP-1 functions such as oxidative damage exacerbations, cellular energetics and apoptosis pathways, regulation of inflammatory mediators, promotion of endothelial dysfunction, and ERK-mediated signaling in pathogenesis. Thrombosis is one such pathogenesis that comprises exacerbation of coagulation cascade due to biochemical alterations in endothelial cells, platelet activation, overexpression of adhesion molecules, cytokines release, and leukocyte adherence. Thus, the activation of endothelial and inflammatory cells in thrombosis implicates a potential role of PARP1 activation in thrombogenesis. This review article explores the direct impact of PARP1 activation in the etiology of thrombosis and discusses PARP1-mediated endothelial dysfunction, inflammation, and epigenetic regulations in the disease manifestation. Understanding PARP1 functions associated with thrombosis may elucidate novel pathogenetic mechanisms and help in better disease management through newer therapeutic interventions targeting PARP1 activity.

CineECG analysis of body surface potential mapping performed in preclinical and clinical plakophilin-2-variant carriers

Abstract Background/introduction Pathogenic variation of the plakophilin-2 (PKP2) gene is associated with arrhythmogenic cardiomyopathy (ACM). Disease manifestation in PKP2-pathogenic variant (PV) carriers differs greatly. Early detection of disease is crucial and could be of benefit in the risk stratification of this population. 67-lead body surface potential mapping (BSPM) could offer more insight into subtle electrical abnormalities. CineECG is a novel tool which can provide an estimation of the average pathway of ventricular activation based on the BSPM-signals, and could be of added value in the detection of electrical abnormalities. Purpose This study aimed to analyze 67-lead BSPM data with CineECG to ascertain the electrical activation pathway in PKP2-PV carriers and to compare these to the normal CineECG. Methods Ten PKP2-PV carriers underwent 67-lead BSPM. Six carriers were without definite ACM diagnosis (preclinical); no Task Force Criteria (TFC) were met apart from the identification of the pathogenic PKP2-variant. The other four carriers were all diagnosed with definite ACM (symptomatic). The average location and direction of ventricular activation was determined with CineECG, resulting in a CineECG trajectory throughout the ventricles. These results were compared to the normal CineECG trajectory, which was established in a previous study with normal ECG’s from the PTB-XL database. A CineECG trajectory that deviated more than 15% from the normal trajectory was considered abnormal. Additionally, to further determine the added diagnostic value of BSPM and CineECG beyond the standard 12-lead ECG, the 12-lead ECG’s were evaluated for abnormalities by three different ECG-experts. Results Expert evaluation of the 12-lead ECG showed that all preclinical PKP2-PV carriers had a normal ECG (no TFC and no other abnormalities such as abnormal electrical heart axis, pathological Q-waves or low voltage). In the symptomatic carriers, all ECG’s showed either presence of TFC or conduction abnormalities. Of the ten PKP2-PV carriers, eight exhibited an abnormal CineECG trajectory. In the preclinical group, four out of six carriers had an abnormal activation trajectory, while all symptomatic carriers had an abnormal CineECG trajectory. Conclusions Through CineECG analysis of 67-lead BSPM, abnormal ventricular activation was identified in the majority of PKP2-PV carriers. Notably, abnormal activation was observed in four out of six preclinical PKP2-PV carriers while the standard 12-lead ECG showed no abnormalities. Future research in a larger group, which also includes follow-up data, is warranted to determine whether these results are an indication of early signs of disease.Figure 1

Oral cavity disorders in traditional, ethnic and original people communities

This chapter describes a worrying scenario and the territory of multidisciplinary health work in Brazil, a diverse country: the knowledge on the part of the dentist and the multidisciplinary team about the health of the black population corresponds to a demand in health, since this group has a predisposition to certain diseases, which if diagnosed early, will be possible to contribute to better therapeutic planning, predictability, and a favorable prognosis in certain clinical manifestations. However, such semiological methodological research may also contribute to the investigation and better understanding of oral cavity disorders that occur in members of traditional communities, in addition to displaced people (indigenous and gypsies), in an urban presence in Rio de Janeiro/Brazil. , envisioning better health outcomes for these vulnerable populations. Periodontal disease can be defined as a multifactorial chronic inflammatory process that affects the protective and supporting tissues of the teeth. Several factors related to this process are currently recognized, such as environmental, genetic, socioeconomic, systemic, ethnic factors and individual susceptibility of the host (very well covered technically by Semiology and repertorization). The manifestations of periodontal disease in people of African descent and the possible causal relationships that make them more susceptible (as described for sickle cell anemia) were presented, thus indicating the need for an individualized preventive approach to this population. Habits that are harmful to the health of the oral cavity were also listed. Finally, we emphasize the culminating point that was the meeting in the health space of the 7th ward of the Homeopathy Service of the Hospital Geral Santa Casa da Misericórdia in Rio de Janeiro, when it was possible to talk about the importance of interventions on habits that compromise the style of life and quality of life also contribute to the emergence of oral cavity neoplasms. The path of health promotion via multidisciplinary health education carried out jointly by professionals who are members of Homeopathy institutions in Rio de Janeiro stood out in relevance.

Analysis of correlative factors of female coronary slow-flow phenomenon: A retrospective study.

The coronary slow-flow phenomenon (CSFP) is a manifestation of coronary artery disease wherein coronary angiography reveals no apparent stenosis; however, there is a delay in blood flow perfusion. Given its increased occurrence in male patients, with the majority of subjects in previous studies being male, this study aimed to explore whether distinct risk factors are present in female patients with CSFP. This single-center retrospective study focused on female patients diagnosed with CSFP by using coronary angiography. Eligible patients meeting the predefined inclusion and exclusion criteria were divided into the study group (presenting with CSFP) and control group (displaying normal epicardial coronary arteries). Comparative analyses of clinical and diagnostic data were performed. Ninety-two patients with CSFP and an equal number of controls were enrolled in this study. Patients with CSFP exhibited a higher prevalence of smokers (P = .017) and a heightened incidence of diabetes mellitus (DM) (P = .007). Significantly elevated levels of total cholesterol (TC) (P = .034) and free fatty acids (FFA) (P = .016) were observed in the CSFP group compared to those in the control group. Additionally, patients with CSFP displayed lower levels of apolipoprotein E (ApoE) (P = .092), free thyroxine (FT4) (P = .001), and total thyroxine (TT4) (P = .025). Logistic regression analysis indicated that smoking (P = .019), FFA (P < .001), ApoE (P = .015), and FT4 (P < .001) were independent risk factors for CSFP, accounting for confounding factors. Additionally, the area under the ROC curve (AUC) of the combined effect of smoking, ApoE, FT4, and FFA on CSFP was 0.793 (95% CI: 0.729-0.857, P < .01). In addition to the established risk factors for smoking, diabetes, and hyperlipidemia, female patients with CSFP exhibited significant differences in apoE, FFA, FT4, and TT4 levels compared to the control group. Smoking, FFA, and FT4 levels emerged as independent risk factors for CSFP.

The impact of comorbidities and substance use on heart failure events and major ventricular arrhythmias in phospholamban p.(Arg14del) positive individuals

Abstract Background Patients with the phospholamban (PLN) p.(Arg14del) variant can develop a severe cardiomyopathy, characterized by progressive heart failure (HF) and major ventricular arrhythmias (VA). However, there is a marked variability in disease expression among affected individuals. There is still a considerable gap of knowledge regarding the influence of comorbidities and substance use on disease progression. Purpose The aim of this study is to investigate whether specific comorbidities and substance use are associated with HF events or major VA events in PLN p.(Arg14del) positive individuals. Method Logistic regression analysis was conducted was conducted in a retrospective cohort of 880 PLN p.(Arg14del) positive individuals (N=847 without heart failure at baseline, N=810 without major arrhythmia at baseline and N=780 without both). Comorbidities and substance use at baseline were assessed in univariable and multivariable models with respect to HF events, major VA events, and a composite endpoint of these two referred to as ‘severe phenotype’. Heart failure was defined as heart failure hospitalization, left ventricle assist device implantation, heart transplantation or HF-related death. Major VA was defined as sustained VA, appropriate implantable cardioverter defibrillator intervention, or (aborted) sudden cardiac death. Results Of all tested comorbidities, only renal dysfunction defined as an eGFR (CKD-EPI) &amp;lt;60 ml/min per 1.73 m² was significantly and independently associated with all endpoints (p&amp;lt;0.001). In the substance use analysis, prior history of smoking was associated with heart failure and a severe phenotype (p&amp;lt;0.002 and p&amp;lt;0.021), however actively smoking was not associated with both endpoints. Conclusion Renal dysfunction and a history of smoking were the only factors identified to be associated with worse outcomes in PLN p.(Arg14del) positive individuals. Whether renal dysfunction signifies a risk factor or an early manifestation of disease has to be further elucidated.

COVID-19 Impact on Female Patients at Tertiary Care Hospital – A Retrospective Study

Objectives: Corona virus disease-19 (COVID-19) has impacted worldwide leading to a high mortality rate. It has been observed that male mortality rate is higher than females due to which it is crucial to systematically study gender differences in disease manifestations. Our study evaluated the association between mortality in COVID-19-positive cases and gender. Materials and Methods: This retrospective study was conducted in the cardiology department at a tertiary care hospital which included 699 patients with a confirmed positive diagnosis of COVID-19 by reverse transcription polymerase chain reaction and &gt;18 years of age. Data from the medical records of the department were collected during an 8-month period (July 2020–February 2021). Results: Of the 699 patients enrolled in the study within 8 months, 232 (33.1%) were female and 467 (66.7%) were male. Female mortality accounted for 18.99% and male mortality 14.56%. Comparing the severity of the disease, 36% of females showed more severe disease presentation. In the course of the disease with treatment, 51.29% of females required oxygen support. Conclusion: This study showed differences in the mortality rate, ventilation support requirement, and severity of disease in COVID-19 affected males and females.

#1196 C3G and ic-MPGN across the life span: findings from the European Rare Kidney Disease Registry

Abstract Background and Aims C3 glomerulopathy (C3G) and immune complex-membranoproliferative glomerulonephritis (ic-MPGN) are two complement-mediated rare kidney disorders affecting both adults and children for which innovative therapies are under development. Due to the low prevalence and difficult diagnosis of the diseases, demographic and kidney outcome data are scarce. To obtain such information, we interrogated the European Rare Kidney Disease Registry (ERKReg), a Pan-European database of patients with rare kidney diseases treated at specialized adult and pediatric nephrology centers. Method Data on all patients diagnosed with C3G or ic-MPGN were extracted from the ERKReg database, to which more than 22, 000 incident and prevalent patients with rare kidney diseases were enrolled between October 2018 and December 2023. After exclusion of 32 patients with reported disease onset prior to 1998 to ensure compliance with contemporaneous diagnostic and treatment standards, 225 C3G and 173 ic-MPGN patients from 32 pediatric and 12 adult nephrology units in 16 European countries were available for analysis. Among these, 20.4% of C3G and 10.4% of ic-MPGN were incident patients who were enrolled either within 3 months of diagnosis or had diagnostic confirmation of suspected disease during prospective follow-up in ERKReg. Kaplan Meier actuarial survival analysis was performed to calculate time to kidney failure. Survival rates are given as median estimates and 95% confidence intervals. The impact of disease type and age at disease onset on kidney survival was assessed by Cox regression analysis. Results Overall, 80.9% of C3G and 33.5% of ic-MPGN patients had disease onset in childhood; the median (IQR) age at diagnosis was 12.4 (8.4-16.2) years for C3G and 38.9 (12.1-57.6) years for ic-MPGN. Genetic variants in CFH, CFHR1/3/5 and CFB were identified in 13 C3G (10.7% of tested) and 4 (14.8% of tested) ic-MPGN patients, and CFH autoantibodies in another 7 (17% of tested) C3G patients. Among the incident patients, 71.7% presented in CKD1 and 6.5% in CKD4/5 for C3G, as compared to 27.8% CKD1 and 27.7% CKD4/5 for ic-MPGN. Nephrotic-range proteinuria was present in 34% of incident C3G and 44% of ic-MPGN patients respectively. At last observation, 7.8% of childhood-onset and 17.1% of adult-onset C3G patients were on kidney replacement therapy (KRT) (thereof 71% and 86% with functioning transplant, respectively). For ic-MPGN at last observation, 14.6% of childhood-onset and 38.9% of adult-onset received KRT (thereof 62.5% and 69.0% with functioning graft, respectively). Kidney survival rates are given in the table below: The risk of progression to kidney failure within the observation period was approximately 60% higher in ic-MPGN vs. C3G (HR: 1.6; CI 95%: 0.9-2.8; p = 0.06) and was twice as high in patients with adult vs. pediatric disease onset (HR: 2.0; CI 95%: 1.2-3.3; P = .01). Conclusion C3G tends to manifest at earlier age than ic-MPGN. Altered complement regulation can be identified in subsets of patients with both disorders. Functional kidney impairment at first disease manifestation is more common and progression to kidney failure occurs more rapidly with ic-MPGN vs. C3G. Disease onset at adult age is associated with a more rapid disease progression compared to childhood-onset disease.

#2199 Kidney involvement aspects in women with Fabry disease from the Romanian cohort

Abstract Background and Aims Fabry disease (FD) is an X-linked rare lysosomal storage disease causing progressive nervous system, kidney and heart disorders. Progressive kidney impairment is common, and an important cause of morbidity and mortality. In FD females, treatment guidelines recommend therapy initiation when there is evidence of organ involvement, but determining the proper moment to start FD specific treatment could be a real challenge in the cases. The aim of our retrospective study is to investigate clinical and histological aspects of kidney involvement in female patients with genetically confirmed FD evaluated in our Expert Center for Rare Diseases of the Reno-Urinary System between 2015–2023, with focus on the clinical phenotype and initiation of FD specific treatment. Method All patients had comprehensive assessment for target organ manifestations of Fabry disease. Renal function was assessed using serum creatinine, albumin creatinine ratio and proteinuria. Also, 14 (40%) FD females underwent kidney biopsy (KB) in order to reveal the FD specific lesions and/or to establish the indication for FD pathogenic therapy. Kidney biopsy specimens were analyzed by light and electron microscopy. Results Our study included 35 heterozygous adult females with FD from 25 unrelated families. Most females (91.4%) were diagnosed through family screening, while 3 females (8.6%) were index cases. The mean age at diagnosis was 43.8 ± 15.3 years (range 17-73 years), although mean age of symptoms onset was 34.3 ± 13.5 years (range 14-61 years). Six women from our cohort were considered healthy carriers, three females presented only neurological manifestations, nine patients had combined renal and neurological involvement, one patient had cardiac and renal involvement and the others presented multiple organ involvement. Significant co-morbidities were: arterial hypertension in 13 patients, diabetes mellitus in 2 patients, and obesity in 9 patients. Overall baseline mean eGFR was 79.9 ± 28.2 (range 25-135) ml/min/1.73 m2. Eleven patients had no obvious kidney involvement, 10 patients presented chronic kidney disease (CKD) stage 2, 11 patients CKD stage 3, one CKD stage 4 and 1 was hemodialyzed. Seventeen patients presented normal UACR, thirteen patients showed microalbuminuria, and four patients presented macroalbuminuria. Overt proteinuria (&amp;gt; 0.3 g/24 h) was noticed in 8 patients. Thirteen females performed KB before the initiation of FD specific treatment, and one patient was already treated. At the moment of KB, five patients had normal biologic kidney assessment, three patients presented CKD stage 2 (microalbuminuria in 2 cases and proteinuria in 1 case), and five patients presented CKD stage 3 (normoalbuminuria in 1 case, microalbuminuria in 1 case and overt proteinuria in 3 cases). All KBs showed lysosomal accumulation in the podocytes, 92.8% showed inclusions in the parietal cells of the Bowman capsule, 85.7% in the tubules, while vascular inclusions were found in 78.5% of cases. Also, we observed segmental glomerular sclerosis in 5 cases, interstitial fibrosis and tubular atrophy in 3 cases, each. Only 2 patients were treated with pathogenic therapy before the first evaluation in our center. After multidisciplinary evaluation, 22 patients (62.8%) from our cohort received recommendation to initiate FD specific treatment, and 11 patients entered in our follow-up program. Evidence of specific FD lesions in KB was a strong reason to support the recommendation to initiate FD specific treatment. Conclusion Our results showed that kidney involvement in FD females can vary from asymptomatic or mildly symptomatic, to severely symptomatic, with end stage kidney disease. Thus, females should be carefully evaluated and monitored in a multidisciplinary team, in order to diagnosed FD affected organs. Also, we underline that a normal standard assessment of the kidney cannot rule out kidney involvement in female patients with FD, and strengthen the importance of KB for detection of early kidney involvement and for additional support for early initiation of FD specific therapy.

#710 Rare manifestation of minimal change disease associated with prostate cancer

Abstract Background and Aims Prostate cancer is the most common malignancy in men. Secondary nephrotic syndrome as part of the paraneoplastic syndrome occurs in 11% of cases and is most often associated with membranous glomerulopathy. The association of minimal change disease (MCD) and prostate cancer is extremely rare, where only one case has been described in the available literature. Method We present the case of a 77-year-old patient who was admitted to the Transplantation-Nephrology Department of the University Hospital Martin with 3rd degree acute kidney injury and anasarca with fully developed nephrotic syndrome. Results During hospitalization, there was a gradual elevation of renal parameters and oliguria with the need for hemodialysis treatment. However, as part of the oncological screening, the level of prostate specific antigen was elevated (10.69 ng/l) with subsequent biopsy confirmed adenocarcinoma of the prostate in stage IIB (pT1cN0M0). Renal biopsy was performed with the finding of MCD, in light microscopy without pathological findings, with fully vital, normocellular glomeruli, without interstitial fibrosis and tubular damage, immunofluorescence without significant findings, in the electron microscope, pedicel podocyte fusions were present. Despite the generally valid recommendations for the treatment of prostate cancer of the given stage and age of the patient (follow-up), antiandrogen therapy was started in cooperation with the urologist along with the treatment of MCD with corticosteroids at a dose of 1 mg/kg. The patient experienced a significant improvement in renal parameters with the onset of diuresis without the need for dialysis treatment. Conclusion In the reported case, we describe a rare form of MCD associated with prostate cancer and a rare manifestation in the form of renal failure and the need for dialysis treatment with subsequent complete restitution of renal functions after KS treatment and antiandrogen treatment of the underlying oncological disease.

#1389 Identification of serum lipidomic profile in nephrotic syndrome patients

Abstract Background and Aims Nephrotic syndrome describes a collection of symptoms, mainly heavy proteinuria leading to kidney function loss, that can be caused by different underlying kidney diseases. Common primary causes of nephrotic syndrome include focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and membranous nephropathy (MN). Nephrotic syndrome is often characterized by plasma lipid abnormalities with elevations in cholesterol, triglycerides and lipoproteins. Here we set out to generate a detailed lipidomic analysis of FSGS, MCD and MN patient's plasma to find lipid changes common to nephrotic syndrome or specific for the underlying disease. Method For this lipidomic study, we included patients with primary FSGS (2 cohorts with n = 5), genetic FSGS (n = 5), MCD (n = 5) and MN (n = 5) in whom serum had been collected at the time they presented at our center with active nephrotic syndrome. We compared the serum lipidome of nephrotic syndrome patients with age matched healthy controls (n = 5), and with age matched patients with familial hypercholesterolemia (n = 5) who, like patients with nephrotic syndrome, have significantly elevated lipid values. Serum was analyzed using the Shotgun Lipidomics platform by Lipotype GmbH (Dresden, Germany), as previously described [1]. Results The lipidomic profile of patients with nephrotic syndrome was markedly different compared to control groups (Fig. 1A). In particular, lower levels of lyso-phophatidylcholine (LPC) and higher concentrations of phosphatidylethanolamine (PE) and lyso-PE (LPE) compared to control groups were most prominent (Fig. 1B). Subspecies analysis identified LPC 16:0;0 to be highly downregulated in patients with nephrotic syndrome (Fig. 2A), whereas LPE 18:0;0 and nearly all PE subspecies were increased compared to control groups (Fig. 2B and C). The lipidomic profile was largely comparable between different underlying diseases and we could not identify lipid classes specifically different for certain diseases. Conclusion Our lipidomic data show that patients with nephrotic syndrome have a distinct lipid profile compared to healthy controls or other disease controls. We identified LPCs, PEs and LPEs to be changed in nephrotic syndrome. We could not identify lipids specific for certain diseases underlying nephrotic syndrome, but rather identified a general nephrotic syndrome lipid profile. This suggests that lipid changes are rather a consequence of disease manifestation in these patients with various underlying causes. Further research should focus on confirming this lipid profile in larger cohorts and unraveling the mechanisms leading to the observed lipid changes.

Beyond the surface: unveiling gaps in medical education through eyes of diverse learners.

Inadequate education regarding disease manifestations in diverse skin colors hinders diagnosis and exacerbates health disparities. All levels of medical trainees report low confidence in accurately identifying disease in skin of color (SOC). To help further elucidate these concerns, our research aims to assess medical student confidence in recognizing cutaneous diseases in SOC and their viewpoints regarding SOC education within their institution. An eight-question, open-ended survey was provided to medical students before and after a SOC presentation. The survey assessed participants' confidence in their diagnostic ability and perspectives on educational material. Among the 70 attendees, 58 (82.8%) and 64 (91.4%) completed the pre- and post-seminar surveys, respectively. There was a significant discrepancy in confidence levels when assessing cutaneous manifestations of internal pathology in light (Monk Skin Colors 1-5) versus dark (Monk Skin Colors 6-10) skin (p < 0.009). Notably, 78.7% (37/47) perceived the institutional learning materials as insufficient for SOC. Post-seminar reflections indicated that 87.2% (40/46) of students lacked confidence in diagnosing SOC, with 78.7% (32/46) citing inadequate curriculum coverage as the cause. An additional 8.5% (6/46) identified the predominance of white-centric medical descriptions as a hindrance. Students collectively called for improved educational approaches, including better visual representation of diseases in darker skin. Medical education must continue to strive for increased SOC representation to train competent physicians in treating a diverse patient population and reduce disparities in SOC patients.